<i>Background:</i> Circulating tumor cells can now be identified in subjects with metastatic melanoma by using the reverse-transcriptase polymerase chain reaction (RT-PCR) to detect the messenger RNA of tyrosinase, a key enzyme of melanogenesis. <i>Aim and Methods:</i> The aim of this study was to determine whether the detection of positive tyrosinase cells in patients at metastatic stage was associated with a worse evolution. 32 patients were included with metastatic melanoma (AJCC IV). <i>Results:</i> 66% had a positive tyrosinase RT-PCR and a shorter survival compared with patients with a negative RT-PCR, but this difference is not statistically significant. However, a positive test could appear indicative of rapid progression and poor prognosis. <i>Conclusion:</i> The prognostic value of this method could be improved by combining it with PCR of other melanoma markers (Melan A, Mage 3) or assays of serum markers (S 100 protein or lactate dehydrogenase).